[Chronology of portal hypertension, decreased sodium excretion, and activation of the renin-angiotensin system in experimental biliary cirrhosis].

OBJECTIVES

1) To evaluate the biochemical, renal, histological and splanchnic and systemic hemodynamic abnormalities induced by bile duct obstruction in rats, and 2) to study the temporal relationships between the start of portal hypertension, decrease of urinary sodium excretion and activation of the renin-angiotensin system.

METHODS

Bile duct obstruction was induced in 127 male Wistar rats, and renal function, hemodynamic, biochemical and liver histology were evaluated at weeks 1, 2, 3 and 4 after complete bile duct obstruction; the data were compared to that in 30 control rats.

RESULTS

Portal pressure significantly increased at week 1 (11.7 +/- 1.5. vs. 7.8 +/- 1.5 mmHg, p < 0.05) while the mean arterial pressure remained stable until week 4 when a slight decrease was observed (91.3 +/- 6.6 vs. 96.1 +/- 8.6 mmHg in control rats). A significant decrease in urinary sodium excretion was observed at week 1 (1.1 +/- 0.5 mEq/24 h) compared to control rats (2.3 +/- 0.6 mEq/24 h). In addition, hyperreninemia was observed at week 1 (5.1 +/- 0.2 vs. 2.4 +/- 1.3 ng Ang l/mL/h, p < 0.05) and hyperaldosteronism at week 2 (103 +/- 46 vs. 25.1 +/- 8.8 ng/24 h, p < 0.05) compared to control rats.

CONCLUSION

A temporal relationship between the beginning of portal hypertension and a decrease of renal sodium excretion, hyperreninemia and hyperaldosteronism was observed in bile duct ligated rats. This experimental model could be used to evaluate the effects of new drugs to prevent biliary cirrhosis including the abnormalities in the renal handling of sodium.